Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team finds mechanism linking key inflammatory marker to cancer

21.05.2013
In a new study described in the journal Oncogene, researchers reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.

Scientists call this Jekyll-and-Hyde molecule NF-kappa B. In healthy cells, it is a powerful “first responder,” a vital part of the body’s immune and inflammatory responses. It spends most of its life in the cell’s cytoplasm, quietly awaiting orders.

But when extracellular signals – of a viral or bacterial invasion, for example – set off chemical alarms, the cell unchains this warhorse, allowing it to go into the nucleus where it spurs a flurry of defensive activity, including the transcription of genes that trigger inflammation, promote cell proliferation and undermine cell death.

Researchers have known for years that a hyperactive form of NF-kappa B that gets into the nucleus and stays there is associated with various cancers. But they didn’t know what was keeping it active in the nucleus.

“Normally in the cell NF-kappa B is in the cytosol, it’s not in the nucleus, and it’s not activated,” said University of Illinois medical biochemistry professor Lin-Feng Chen, who led the new study.

“You have to stimulate normal cells to see NF-kappa B in the nucleus. But in cancer cells without any stimulation you can see this nuclear form of NF-kappa B. The cell just won’t die because of this. That is why NF-kappa B is so important in cancer.”

In the new study, Chen’s group found that another molecule known to help regulate gene expression, called BRD4, recognizes a specific amino acid on a subunit of the NF-kappa B protein complex after the amino acid has been marked with a specific tag, called an acetyl group. This “acetylation” allows the BRD4 to bind to NF-kappa B, activating it and preventing its degradation in cancer cells.

Previous studies had shown that BRD4’s recognition of the acetylated subunit increased NF-kappa B activation, but this recognition had not been linked to cancer.

BRD4 belongs to a class of molecules that can recognize chemical markers on other proteins and interact with them to spur the marked proteins to perform new tasks. Chemical “readers” such as BRD4 are important players in the field of epigenetics, which focuses on how specific genes are regulated.

“In epigenetics, there are writers, there are readers and there are erasers,” Chen said. The writers make modifications to proteins after they are formed, without changing the underlying sequence of the gene that codes for them. These modifications (such as acetylation) signal other molecules (the readers) to engage with the marked proteins in various ways, allowing the proteins to fulfill new roles in the life of the cell. Epigenetic erasers remove the marks when they are no longer of use.

Such protein modifications “have been shown to be critically involved in transcription regulation and cancer development,” the researchers report.

To test whether BRD4 was contributing to the sustained presence of NF-kappa B in the nucleus of cancer cells, Chen and his colleagues exposed lung cancer cells in cell culture and in immune-deficient mice to JQ1, a drug that interferes with BRD4 activity.

Exposure to JQ1 blocked the interaction of BRD4 and NF-kappa B, blocked the expression of genes regulated by NF-kappa B, reduced proliferation of lung cancer cells and suppressed the ability of lung cancer cells to induce tumors in immune-deficient mice, the researchers found.

The researchers also discovered that depletion of BRD4 or the treatment of cells with JQ1 induced the degradation of the NF-kappa B subunit recognized by BRD4.

Chen said that BRD4 likely prevents other molecules from recognizing the hyperactive NF-kappa B in the nucleus and marking it for degradation.

“This is an example of how epigenetic regulators and NF-kappa B may one day be targeted for the treatment of cancer,” he said.

Researchers from Illinois biochemistry professor Satish Nair’s laboratory and from the laboratory of James Bradner at the Dana-Farber Cancer Institute contributed to this study.

Editor’s notes: To reach Lin-Feng Chen, call 217-333-7764;
email lfchen@illinois.edu.
The paper, “BRD4 Maintains Constitutively Active NF-''B in Cancer Cells by Binding to Acetylated RelA,” is available online or from the U. of I. News Bureau

Diana Yates | University of Illinois
Further information:
http://www.illinois.edu

More articles from Life Sciences:

nachricht Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

Climate change: In their old age, trees still accumulate large quantities of carbon

17.08.2017 | Earth Sciences

Modern genetic sequencing tools give clearer picture of how corals are related

17.08.2017 | Life Sciences

Superconductivity research reveals potential new state of matter

17.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>